Zou Zihua, Wu Lige, Hao Xuezhi, Li Yan, Liang Li, Gu Yangchun, Ying Jianming, Li Junling, Xing Puyuan
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, Fujian Cancer Hospital, Clinical Oncology School of Fujian Medical University, Fuzhou, China.
Thorac Cancer. 2025 Jan;16(2):e70000. doi: 10.1111/1759-7714.70000.
The clinical implications of different EML4-ALK fusion variants remain poorly elucidated in the era of second-generation ALK inhibitors.
This was a retrospective cohort study, wherein patients diagnosed with locally advanced or metastatic non-small cell lung cancer harboring EML4-ALK fusion were stratified into two cohorts based on their first-line treatment: Cohort 1 received alectinib, while Cohort 2 received crizotinib. Statistical analysis was employed to investigate the impact of different EML4-ALK variants and TP53 status on the efficacy of first-line ALK-TKIs.
Finally, 49 patients were enrolled in cohort 1 and 53 patients in cohort 2. In cohort 1, patients with long EML4-ALK fusion variants exhibited prolonged PFS (NR vs. 34.0 m, p = 0.004, HR = 0.30, 95% CI: 0.12-0.74) and an elevated 5-year OS rate (93.3% vs. 68.4%, p = 0.020, HR = 0.12, 95% CI: 0.02-0.62) compared to those with short variants. The median PFS was not reached in TP53-wt group and 47.0 m in TP53-mut group (p = 0.087, HR = 0.44, 95% CI: 0.17-1.17). The TP53-wt group exhibited a superior 5-year OS rate (100% vs. 77.8%, p = 0.030) compared to TP53-mut group. In cohort 2, the median PFS was 14.0 m in long variant group and 12.9 m in short variant group (p = 0.094, HR = 0.65, 95% CI: 0.37-1.13); the median OS was not reached in long variant group and 69.2 m in short variant group (p = 0.254, HR:0.62, 95% CI: 0.27-1.42). However, the efficacy of first-line crizotinib did not appear to be influenced by the TP53 status.
EML4-ALK short variants and TP53 mutations are both adverse factors for first-line alectinib efficacy, but they have little effect on first-line crizotinib.
在第二代ALK抑制剂时代，不同EML4-ALK融合变体的临床意义仍未得到充分阐明。
这是一项回顾性队列研究，其中诊断为携带EML4-ALK融合的局部晚期或转移性非小细胞肺癌患者根据其一线治疗分为两个队列：队列1接受阿来替尼治疗，而队列2接受克唑替尼治疗。采用统计分析来研究不同EML4-ALK变体和TP53状态对一线ALK-TKIs疗效的影响。
最终，队列1纳入49例患者，队列2纳入53例患者。在队列1中，与携带短EML4-ALK融合变体的患者相比，携带长EML4-ALK融合变体的患者表现出更长的无进展生存期（未达到 vs. 34.0个月，p = 0.004，HR = 0.30，95% CI：0.12 - 0.74）和更高的5年总生存率（93.3% vs. 68.4%，p = 0.020，HR = 0.12，95% CI：0.02 - 0.62）。TP53野生型组未达到中位无进展生存期，TP53突变组为47.0个月（p = 0.087，HR = 0.44，95% CI：0.17 - 1.17）。与TP53突变组相比，TP53野生型组表现出更高的5年总生存率（100% vs. 77.8%，p = 0.030）。在队列2中，长变体组的中位无进展生存期为14.0个月，短变体组为12.9个月（p = 0.094，HR = 0.65，95% CI：0.37 - 1.13）；长变体组未达到中位总生存期，短变体组为69.2个月（p = 0.254，HR：0.62，95% CI：0.27 - 1.42）。然而，一线克唑替尼的疗效似乎不受TP53状态的影响。
EML4-ALK短变体和TP53突变均是一线阿来替尼疗效的不利因素，但它们对一线克唑替尼的影响较小。
